{"id":"https://openalex.org/W2575748829","doi":"https://doi.org/10.1182/blood.v126.23.670.670","title":"Pathophysiology of Macrocytic Anemia in Diamond Blackfan Anemia and Del(5q) Myelodysplastic Syndrome","display_name":"Pathophysiology of Macrocytic Anemia in Diamond Blackfan Anemia and Del(5q) Myelodysplastic Syndrome","publication_year":2015,"publication_date":"2015-12-03","ids":{"openalex":"https://openalex.org/W2575748829","doi":"https://doi.org/10.1182/blood.v126.23.670.670","mag":"2575748829"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v126.23.670.670","doi":"https://doi.org/10.1182/blood.v126.23.670.670","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v126.23.670.670","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5101855925","display_name":"Zhantao Yang","orcid":"https://orcid.org/0000-0002-3259-4400","observed_orcids":["https://orcid.org/0000-0002-3259-4400"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Zhantao Yang","raw_affiliation_strings":["Medicine/Hematology, University of Washington, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Medicine/Hematology, University of Washington, Seattle, WA","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5091777632","display_name":"Sio\u1e03\u00e1n Keel","orcid":"https://orcid.org/0000-0002-9599-8226","observed_orcids":["https://orcid.org/0000-0002-9599-8226"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sioban B. Keel","raw_affiliation_strings":["Medicine/Hematology, University of Washington, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Medicine/Hematology, University of Washington, Seattle, WA","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5013754928","display_name":"Brent Lee Wood","orcid":"https://orcid.org/0000-0001-7414-3969","observed_orcids":["https://orcid.org/0000-0001-7414-3969"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Brent L. Wood","raw_affiliation_strings":["Laboratory Medicine, University of Washington, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory Medicine, University of Washington, Seattle, WA","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074629157","display_name":"Bart Lee Scott","orcid":"https://orcid.org/0000-0001-9620-7839","observed_orcids":["https://orcid.org/0000-0001-9620-7839"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]},{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Bart L. Scott","raw_affiliation_strings":["Medical Oncology, Fred Hutchinson Cancer Research Center & University of Washington, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Medical Oncology, Fred Hutchinson Cancer Research Center & University of Washington, Seattle, WA","institution_ids":["https://openalex.org/I201448701","https://openalex.org/I4210089486"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5055816987","display_name":"Janis L. Abkowitz","orcid":"https://orcid.org/0000-0002-1820-5341","observed_orcids":["https://orcid.org/0000-0002-1820-5341"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Janis L. Abkowitz","raw_affiliation_strings":["Medicine/Hematology, University of Washington, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Medicine/Hematology, University of Washington, Seattle, WA","institution_ids":["https://openalex.org/I201448701"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5101855925"],"corresponding_institution_ids":["https://openalex.org/I201448701"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":{"value":0.23124639,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":90,"max":94},"biblio":{"volume":"126","issue":"23","first_page":"670","last_page":"670"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12919","display_name":"Blood disorders and treatments","score":0.5673999786376953,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12919","display_name":"Blood disorders and treatments","score":0.5673999786376953,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.25540000200271606,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10345","display_name":"Hematopoietic Stem Cell Transplantation","score":0.025499999523162842,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/diamond-blackfan-anemia","display_name":"Diamond-Blackfan anemia","score":0.9089999794960022},{"id":"https://openalex.org/keywords/del-5q-myelodysplastic-syndrome","display_name":"del(5q) myelodysplastic syndrome","score":0.9929999709129333},{"id":"https://openalex.org/keywords/macrocytic-anemia","display_name":"macrocytic anemia","score":0.9980000257492065},{"id":"https://openalex.org/keywords/ribosome-assembly","display_name":"ribosome assembly","score":0.8669999837875366},{"id":"https://openalex.org/keywords/erythropoiesis","display_name":"erythropoiesis","score":0.7879999876022339},{"id":"https://openalex.org/keywords/heme-biosynthesis","display_name":"heme biosynthesis","score":0.7960000038146973},{"id":"https://openalex.org/keywords/globin-synthesis","display_name":"globin synthesis","score":0.8270000219345093},{"id":"https://openalex.org/keywords/erythroid-precursors","display_name":"erythroid precursors","score":0.6050000190734863},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.45500001311302185},{"id":"https://openalex.org/keywords/p53-signaling-pathway","display_name":"p53 pathway","score":0.7310000061988831},{"id":"https://openalex.org/keywords/alas2","display_name":"ALAS2","score":0.5910000205039978}],"concepts":[{"id":"https://openalex.org/C2778997081","wikidata":"https://www.wikidata.org/wiki/Q1208654","display_name":"Diamond\u2013Blackfan anemia","level":5,"score":0.9173873662948608},{"id":"https://openalex.org/C68838962","wikidata":"https://www.wikidata.org/wiki/Q852654","display_name":"Haploinsufficiency","level":4,"score":0.7811485528945923},{"id":"https://openalex.org/C2777550742","wikidata":"https://www.wikidata.org/wiki/Q2070695","display_name":"Macrocytic anemia","level":3,"score":0.6452240347862244},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.626502513885498},{"id":"https://openalex.org/C2779703530","wikidata":"https://www.wikidata.org/wiki/Q837174","display_name":"Erythropoiesis","level":3,"score":0.5357024073600769},{"id":"https://openalex.org/C2780007613","wikidata":"https://www.wikidata.org/wiki/Q546523","display_name":"Bone marrow","level":2,"score":0.5013935565948486},{"id":"https://openalex.org/C2778248108","wikidata":"https://www.wikidata.org/wiki/Q5445","display_name":"Anemia","level":2,"score":0.476350337266922},{"id":"https://openalex.org/C2778403015","wikidata":"https://www.wikidata.org/wiki/Q1404923","display_name":"Reticulocyte","level":4,"score":0.47495245933532715},{"id":"https://openalex.org/C109159458","wikidata":"https://www.wikidata.org/wiki/Q919283","display_name":"Haematopoiesis","level":3,"score":0.44141340255737305},{"id":"https://openalex.org/C125996951","wikidata":"https://www.wikidata.org/wiki/Q412234","display_name":"Globin","level":3,"score":0.41128382086753845},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.30782559514045715},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.29648494720458984},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.20247739553451538},{"id":"https://openalex.org/C28328180","wikidata":"https://www.wikidata.org/wiki/Q48196","display_name":"Stem cell","level":2,"score":0.19491857290267944},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.18601304292678833},{"id":"https://openalex.org/C88478588","wikidata":"https://www.wikidata.org/wiki/Q42244","display_name":"Ribosome","level":4,"score":0.17893248796463013},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.10722407698631287},{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.0953148603439331},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v126.23.670.670","doi":"https://doi.org/10.1182/blood.v126.23.670.670","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v126.23.670.670","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9476000070571899,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W3143005659","https://openalex.org/W2359149763","https://openalex.org/W2533445065","https://openalex.org/W2587145799","https://openalex.org/W3145215983","https://openalex.org/W7171859404","https://openalex.org/W2566690647","https://openalex.org/W4405043995","https://openalex.org/W3016303627","https://openalex.org/W2592410029"],"abstract_inverted_index":{"Abstract":[0],"Twenty-five":[1],"percent":[2],"of":[3,12,18,25,98,321,348,411,451,459,474,523,562,657],"Diamond":[4],"Blackfan":[5],"anemia":[6,24,44,647],"(DBA)":[7],"cases":[8],"result":[9,485],"from":[10,16,29,144,199,217,367,487],"haploinsufficiency":[11],"RPS19":[13,211],"and":[14,87,101,104,127,147,158,171,180,194,213,220,236,244,247,251,255,277,290,294,323,332,360,379,387,420,422,426,461,491,502,538,556,619,636],"~30%":[15],"haploinsufficiencies":[17],"other":[19,66,218],"ribosomal":[20],"proteins.":[21],"The":[22,47,594],"macrocytic":[23,43],"del(5q)":[26,88,148,221,272,368,427,462,557],"MDS":[27,89,149,222,273,369,428,463,558,649],"results":[28],"RPS14":[30],"haploinsufficiency.":[31],"When":[32],"tested,":[33],"these":[34,341,441,610],"mutations":[35,628],"disrupt":[36],"ribosome":[37,108],"assembly,":[38],"yet":[39],"how":[40],"this":[41,186,563],"causes":[42],"remains":[45],"uncertain.":[46],"dominant":[48],"hypothesis":[49],"is":[50,62,75,133,249],"that":[51,85,93,106,154,160,184,230,252,267,344,587,598,615],"P53":[52,514,552],"pathway":[53],"activation":[54,553],"leads":[55,110],"to":[56,77,83,111,114,118,190,262,275,285,287,376,484,517,529,549,646,659],"cell":[57,100,135,162,274,457,472,504],"apoptosis,":[58],"however,":[59],"why":[60],"erythropoiesis":[61,588],"severely":[63],"impacted,":[64],"while":[65,240,401,469],"hematopoietic":[67],"as":[68,70,423],"well":[69],"non-hematopoietic":[71],"cells":[72,183,257,283,302,315,346,374,429,501,516,567,579],"function":[73],"appropriately,":[74],"difficult":[76],"explain.":[78],"These":[79],"observations":[80,548],"led":[81],"us":[82],"predict":[84],"DBA":[86,145,202,219,270,301,331,345,425,460,555,565],"share":[90],"a":[91,204,269,448,493,525],"pathogenesis":[92],"reflects":[94],"the":[95,182,200,264,319,335,455,470,521],"rapid":[96],"kinetics":[97],"red":[99],"hemoglobin":[102],"production,":[103,640],"specifically":[105],"poor":[107],"assembly":[109],"an":[112],"inability":[113],"quickly":[115],"translate":[116],"mRNA":[117,246,311,325,385,391,576],"protein,":[119],"delayed":[120],"globin":[121,241,402,639],"synthesis":[122,232,339,352,398],"in":[123,152,292,328,498,554,580,648],"early":[124],"erythroid":[125,156,456,471],"precursors,":[126],"excess":[128,259],"heme.":[129,260],"Since":[130,318,626],"free":[131],"heme":[132,231,338,351,362,397,452,591,600,622,641],"toxic,":[134],"death":[136,482],"ensues.":[137],"To":[138],"explore":[139],"this,":[140],"we":[141,228,280],"studied":[142],"marrow":[143,198,216,412,566],"(n=3)":[146],"(n=6)":[150],"patients":[151,223,225,370,650],"cultures":[153,413,464,477],"optimize":[155],"differentiation":[157],"showed":[159],"(a)":[161],"numbers":[163],"significantly":[164],"decrease":[165],"between":[166],"stages":[167,191,288,377],"I":[168,254,330],"(lin-CD71+CD36-GlyA-)(BFU-E/early":[169],"CFU-E)":[170],"II,":[172],"(lin-CD71+CD36+GlyA-)(CFU-E/early":[173],"proerythroblasts;":[174],"Li":[175],"et":[176,507,542],"al.":[177,508,543],"Blood":[178],"2014;124:3636);":[179],"(b)":[181],"survive":[185,276],"insult":[187],"differentiate":[188],"normally":[189,239],"III":[192,289,378],"(lin-CD36+GlyA+)":[193],"IV":[195,291,380],"(lin-CD36-GlyA+).":[196],"Using":[197],"index":[201],"patient,":[203],"28-year":[205],"old":[206],"transfusion-dependent":[207],"female":[208],"with":[209,440,444],"inherited":[210],"haploinsufficiency,":[212],"(as":[214],"available)":[215],"(n=2-7":[224],"per":[226],"study),":[227],"demonstrated":[229],"(assessed":[233],"by":[234,408,465,479,519,605],"ALAS2mRNA":[235],"protein)":[237,248],"initiates":[238,404],"production":[242,403],"(\u03b1-":[243],"\u03b2-globin":[245],"slowed,":[250],"stage":[253,329],"II":[256],"have":[258,381,572],"Next,":[261],"discern":[263],"cell-specific":[265],"characteristics":[266],"allow":[268],"or":[271,356,604,634],"fully":[278],"mature,":[279],"compared":[281],"those":[282],"able":[284],"advance":[286],"patient":[293],"concurrent":[295,475],"control":[296,314,333,394,476,578],"cultures.":[297],"Stage":[298],"III-IV":[299],"GlyA+":[300,313],"expressed":[303],"2.4-fold":[304],"less":[305,354,383,530,533,536,539,574],"ALAS2":[306,322,384],"mRNAand":[307],"2-fold":[308],"more":[309],"FLVCR":[310,324,390],"than":[312,393,577],"(p":[316,467],"values<0.05).":[317],"levels":[320],"were":[326],"similar":[327,372],"cells,":[334],"time":[336],"when":[337,590],"initiates,":[340],"data":[342,512,595],"imply":[343],"capable":[347],"down-regulating":[349],"their":[350],"(have":[353,358],"ALAS2)":[355],"content":[357],"moreFLVCR":[359],"increased":[361,434],"export)":[363],"preferentially":[364],"survive.":[365],"Data":[366],"are":[371],"-":[373],"progressing":[375],"2.9-fold":[382],"(p<0.05)":[386],"9.4-fold":[388],"higher":[389],"(p<0.01)":[392],"cells.":[395],"That":[396],"proceeds":[399],"normally,":[400],"slowly,":[405],"was":[406],"confirmed":[407],"sequential":[409],"sampling":[410],"at":[414,430,568],"days":[415],"3,":[416],"7,":[417],"10,":[418],"13,":[419],"17;":[421],"expected,":[424],"day":[431,570],"7":[432],"had":[433],"reactive":[435],"oxygen":[436],"species":[437],"(ROS).":[438],"Consistent":[439],"observations,":[442],"treatment":[443],"10":[445,571],"\u03bcM":[446],"succinylacetone,":[447],"specific":[449],"inhibitor":[450],"synthesis,":[453,535,601],"improved":[454],"output":[458,473],"68-95%":[466],"values<0.05),":[468],"decreased":[478],"4-13%.":[480],"Cell":[481,509],"appears":[483],"both":[486],"apoptosis":[488],"(not":[489],"shown)":[490],"ferroptosis,":[492],"ROS-induced":[494],"process":[495],"previously":[496],"characterized":[497],"kidney":[499],"epithelial":[500],"cancer":[503],"lines":[505],"(Dixon":[506],"2012;149:1060).":[510],"Recent":[511],"showing":[513],"sensitizes":[515],"ferroptosis":[518],"impeding":[520],"transcription":[522,633],"SCL7A11,":[524],"cysteine-glutamate":[526],"antiporter,":[527],"leading":[528],"cysteine":[531],"uptake,":[532],"GSH":[534],"GPX4,":[537],"antioxidants":[540],"(Jiang":[541],"Nature":[544],"2015;520:57)":[545],"link":[546],"our":[547,584],"work":[550],"implicating":[551],"anemia.":[559],"In":[560],"support":[561],"connection,":[564],"culture":[569],"57%":[573],"SLC7A11":[575],"preliminary":[581],"experiments.":[582],"Together,":[583],"studies":[585],"demonstrate":[586],"fails":[589],"exceeds":[592],"globin.":[593],"also":[596,644],"suggest":[597],"decreasing":[599,621],"either":[602],"directly":[603],"chelating":[606],"iron,":[607],"may":[608],"improve":[609],"anemias.":[611],"They":[612],"further":[613],"argue":[614],"lenalidomide":[616],"(destabilizes":[617],"P53)":[618],"therapies":[620],"should":[623],"be":[624],"synergistic.":[625],"diverse":[627],"could":[629],"impede":[630],"brisk":[631,638],"protein":[632],"translation,":[635],"hence":[637],"toxicity":[642],"might":[643],"contribute":[645],"without":[651],"del(5q).":[652],"Disclosures":[653],"No":[654],"relevant":[655],"conflicts":[656],"interest":[658],"declare.":[660]},"counts_by_year":[{"year":2025,"cited_by_count":1}],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2017-01-26T00:00:00"}